title: The Prognostic Value of p16 Hypermethylation in Cancer: A Meta-Analysis.
abstract: The prognostic value of p16 promoter hypermethylation in cancers has been evaluated for several years while the results remain controversial. We thus performed a systematic review and meta-analysis of studies assessing the impact of p16 methylation on overall survival (OS) and disease-free survival (DFS) to clarify this issue.
  
  
  
  We searched Pubmed, Embase and ISI web of knowledge to identify studies on the prognostic impact of p16 hypermethylation in cancers. A total of 6589 patients from 45 eligible studies were included in the analysis. Pooled hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated to estimate the effect using random-effects model.
  
  
  
  The analysis indicated that p16 hypermethylation had significant association with poor OS of non-small cell lung cancer (NSCLC) (HR 1.74, 95% CI: 1.36-2.22) and colorectal cancer (CRC) (HR 1.80; 95% CI 1.27-2.55). Moreover, the significant correlation was present between p16 hypermethylation and DFS of NSCLC (HR 2.04, 95% CI: 1.19-3.50) and head and neck cancer (HR 2.24, 95% CI: 1.35-3.73). Additionally, in the analysis of the studies following REMARK guidelines more rigorously, p16 hypermethylation had unfavorable impact on OS of NSCLC (HR 1.79, 95% CI: 1.35-2.39) and CRC (HR 1.96, 1.16-3.34), and on DFS of NSCLC (HR 2.12, 95% CI: 1.21-3.72) and head and neck cancer (HR 2.24, 95% CI: 1.35-3.73).
  
  
  
  p16 hypermethylation might be a predictive factor of poor prognosis in some surgically treated cancers, particularly in NSCLC.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiang-Bin
authors.initials: XB
authors.lastname: Xing
authors.forename: Wei-Bin
authors.initials: WB
authors.lastname: Cai
authors.forename: Liang
authors.initials: L
authors.lastname: Luo
authors.forename: Long-Shan
authors.initials: LS
authors.lastname: Liu
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Shi
authors.forename: Min-Hu
authors.initials: MH
authors.lastname: Chen
mesh_terms: D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D011237:Predictive Value of Tests; D015996:Survival Rate
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm